This is a request for 5 years of funding through the Mentored Research Scientist Development Award (K01) mechanism. The applicant, Dr. Colleen Hanlon, is a neurobiologist with experience using functional magnetic resonance imaging to examine neural networks affected in chronic cocaine users. To further characterize changes in cortical activity in cocaine users, this application proposes a program of training in diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS). The long- term goal of the applicant is to become an independent investigator, skilled in the application of multiple imaging modalities that may be used to guide treatment strategies in substance abusing populations. The training plan includes structured training courses in TMS acquisition and analysis, DTI image analysis, and multivariate statistics, as well as ongoing training by a team of mentors. Career development is also a strong component of this application with time devoted to Training in the Responsible Conduct of Research, manuscript and grant writing, mentoring students, attendance at scientific meetings, and interactions with the institutional review board. The research component of this award extends prior NIH-funded research complete by Dr. Hanlon, and has been carefully designed to parallel the training plan. The overarching goal of this proposal is to determine the extent to which changes in corpus callosum integrity (Specific Aim #1) and cortical inhibitory tone (Specific Aim #2) are related to atypical BOLD signal changes in the cortex of chronic cocaine users. In addition to extending investigations on sensorimotor laterality, the impact of loss of cortical laterality on cognitive function in cocaine users will also be addressed (Specific Aim #3). These experiments will reveal the extent to which changes in cortical inhibitory tone and corpus callosal integrity may contribute to neurofunctional and behavioral deficiencies in chronic cocaine users. The results of these experiments will be used to further the investigation and development of therapeutic treatment strategies in stimulant dependent individuals. PUBLIC HEALTH RELEVANCE: This is a request for 5 years of funding through the Mentored Research Scientist Development Award (K01) mechanism. The applicant, Dr. Colleen Hanlon, is a neurobiologist with experience using functional magnetic resonance imaging to examine neural networks affected in chronic cocaine users. To further characterize changes in cortical activity in cocaine users, this application proposes a program of training in diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS). The long- term goal of the applicant is to become an independent investigator, skilled in the application of multiple imaging modalities that may be used to guide treatment strategies in substance abusing populations. The training plan includes structured training courses in TMS acquisition and analysis, DTI image analysis, and multivariate statistics, as well as ongoing training by a team of mentors. Career development is also a strong component of this application with time devoted to Training in the Responsible Conduct of Research, manuscript and grant writing, mentoring students, attendance at scientific meetings, and interactions with the institutional review board. The research component of this award extends prior NIH-funded research complete by Dr. Hanlon, and has been carefully designed to parallel the training plan. The overarching goal of this proposal is to determine the extent to which changes in corpus callosum integrity (Specific Aim #1) and cortical inhibitory tone (Specific Aim #2) are related to atypical BOLD signal changes in the cortex of chronic cocaine users. In addition to extending investigations on sensorimotor laterality, the impact of loss of cortical laterality on cognitive function in cocaine users will also be addressed (Specific Aim #3). These experiments will reveal the extent to which changes in cortical inhibitory tone and corpus callosal integrity may contribute to neurofunctional and behavioral deficiencies in chronic cocaine users. The results of these experiments will be used to further the investigation and development of therapeutic treatment strategies in stimulant dependent individuals.